Is PRSS12 p.Pro223= (c.669G>T) pathogenic?

PRSS12 p.Pro223= (c.669G>T) is classified Likely benign in PRSS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-01). Absent from gnomAD v4.1.

How common is PRSS12 p.Pro223= (c.669G>T) in the general population?

PRSS12 p.Pro223= (c.669G>T) is absent from gnomAD v4.1 (gnomAD).

PRSS12 p.Pro223=

c.669G>T · rs151271524 · VCV1176038

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.5	GERP -3.6
Overall
CADD	0.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRSS12
Protein: p.Pro223=
Coding: c.669G>T
MANE Select: NM_003619
dbSNP: rs151271524
Type: single nucleotide variant
Location: chr4:118335624 (GRCh38)
Gene constraint: LOEUF 0.965 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 223: a disulfide bond; the srcr 1 domain

Full PRSS12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRSS12 c.2320+6G>C Uncertain significance ★★ same type
PRSS12 c.821-1G>A Uncertain significance ★★ same type
PRSS12 c.*1615C>T Uncertain significance ★★ same type
PRSS12 c.*221A>T Uncertain significance ★★ same type
PRSS12 p.Ala547Asp Uncertain significance ★★ ⚠ same type
PRSS12 p.Ala79Pro Uncertain significance ★★ ⚠ same type
PRSS12 p.Arg292Trp Uncertain significance ★★ ⚠ same type
PRSS12 p.Arg426Gln Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/prss12-p-pro223 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown